A Novel Inherently Radiopaque Bead for Transarterial Embolization to Treat Liver Cancer - A Pre-clinical Study

Abstract

Purpose: Embolotherapy using microshperes is currently performed with soluble contrast to aid in visualization. However, administered payload visibility dimishes soon after delivery due to soluble contrast washout, leaving the radiolucent bead's location unknown. The objective of our study was to characterize inherently radiopaque beads (RO Beads) in terms of physicomechanical properties, deliverability and imaging visibility in a rabbit VX2 liver tumor model.Materials and Methods: RO Beads, which are based on LC Bead® platform, were compared to LC Bead. Bead size (light microscopy), equilibrium water content (EWC), density, X-ray attenuation and iodine distribution (micro-CT), suspension (settling times), deliverability and in vitro penetration were investigated. Fifteen rabbits were embolized with either LC Bead or RO Beads + soluble contrast (iodixanol-320), or RO Beads+dextrose. Appearance was evaluated with fluoroscopy, X-ray single shot, cone-beam CT (CBCT).Results: Both bead types had a similar size distribution. RO Beads had lower EWC (60-72%) and higher density (1.21-1.36 g/cc) with a homogeneous iodine distribution within the bead's interior. RO Beads suspension time was shorter than LC Bead, with durable suspension (>5 min) in 100% iodixanol. RO Beads ≤300 µm were deliverable through a 2.3-Fr microcatheter. Both bead types showed similar penetration. Soluble contrast could identify target and non-target embolization on fluoroscopy during administration. However, the imaging appearance vanished quickly for LC Bead as contrast washed-out. RO Beads+contrast significantly increased visibility on X-ray single shot compared to LC Bead+contrast in target and non-target arteries (P=0.0043). Similarly, RO beads demonstrated better visibility on CBCT in target arteries (P=0.0238) with a trend in non-target arteries (P=0.0519). RO Beads+dextrose were not sufficiently visible to monitor embolization using fluoroscopy.Conclusion: RO Beads provide better conspicuity to determine target and non-target embolization compared to LC Bead which may improve intra-procedural monitoring and post-procedural evaluation of transarterial embolization.

Characterization of a novel intrinsically radiopaque Drug-eluting Bead for image-guided therapy: DC Bead LUMI™

“…7(A+B) clearly show for the first time, the presence of Dox-loaded DC Bead LUMI ™ in the arterial vasculature surrounding the tumor. The tumor vessels are relatively small in this model and few beads penetrated within the tumor interior, as seen previously with this tumor model [18]; although the area of the tumor was seen not to enhance to the same degree as the surrounding parenchyma, suggesting its arterial supply had been successfully devitalized. As expected in this model, because the procedure was performed to maximise the amount of beads delivered into the liver, filling of both tumor-feeding and non-target vessels was clearly evident from the 3D reconstruction in Fig 7(B).…”

“…The density increases slightly further for both beads when loaded with either doxorubicin or irinotecan, as water is displaced from the hydrogel structure and is replaced by drug. This increase in solids content means that DC Bead LUMI ™ is two orders of magnitude stiffer to compress than DC Bead ™ (Table 2), although this is unlikely to impact on the depth of penetration into vessels as we have previously demonstrated with bench penetration testing [18]. Likewise, administration through microcatheters remains unproblematic with these sizes of beads (Table 3), provided the appropriate bead dilution is maintained.…”

“…The method used was based on that recently reported in detail elsewhere [18] in which the elastic modulus was calculated using a UMIS 2000 nanoindentation system (CSIRO Instruments, Lindfield NSW, Australia) operated by IBIS software (Force range 0.01mN-45mN; displacement range 1nm-100μm). Individual beads of known diameter were compressed under saline (unloaded) or deionized water (drug-loaded) at a constant strain rate (~1–2%/s) generating a force displacement curve that was analyzed for peak modulus values (N = 20).…”

“…This posed some technical challenges, as the presence of such hydrophobic moieties within the hydrogel structure of DC Bead ™ resulted in unusual behaviour that was deleterious to the bead properties. These issues were eventually overcome in order to arrive at a RO DEB that can be handled and administered as in normal clinical practice [18, 19], has excellent drug elution properties and good levels of radiodensity to be usefully imaged under a range of different imaging modalities. Here we report on the characterization of this novel, intrinsically radiopaque DEB, DC Bead LUMI ™ .…”

Interventional Oncology in Hepatocellular Carcinoma

“…21-23 On the other hand, because the LUMI™ beads enable direct visualization of bead location, It may be possible in the future to assess efficacy (i.e., completeness of target tissue embolization) and safety (i.e., unintentional embolization of non-target tissue) (Figure 1). Compared to conventional beads, LUMI™ beads have been shown to allow for better conspicuity to determine target and non-target embolization in pre-clinical studies 24 and to enable real-time geographic localization of embolization during treatment; 25 these results suggest that LUMI™ beads may help determine embolization endpoints more effectively. The imaging characteristics of LUMI™ beads are now studied in an ongoing clinical trial of hepatic tumors (NCT 02649868).…”